Essential role of intracellular glutathione in controlling ascorbic acid transporter expression and function in rat hepatocytes and hepatoma cells

Free Radical Biology & Medicine
Lorena MardonesC I Rivas

Abstract

Although there is in vivo evidence suggesting a role for glutathione in the metabolism and tissue distribution of vitamin C, no connection with the vitamin C transport systems has been reported. We show here that disruption of glutathione metabolism with buthionine-(S,R)-sulfoximine (BSO) produced a sustained blockade of ascorbic acid transport in rat hepatocytes and rat hepatoma cells. Rat hepatocytes expressed the Na(+)-coupled ascorbic acid transporter-1 (SVCT1), while hepatoma cells expressed the transporters SVCT1 and SVCT2. BSO-treated rat hepatoma cells showed a two order of magnitude decrease in SVCT1 and SVCT2 mRNA levels, undetectable SVCT1 and SVCT2 protein expression, and lacked the capacity to transport ascorbic acid, effects that were fully reversible on glutathione repletion. Interestingly, although SVCT1 mRNA levels remained unchanged in rat hepatocytes made glutathione deficient by in vivo BSO treatment, SVCT1 protein was absent from the plasma membrane and the cells lacked the capacity to transport ascorbic acid. The specificity of the BSO treatment was indicated by the finding that transport of oxidized vitamin C (dehydroascorbic acid) and glucose transporter expression were unaffected by BSO treatment. Moreo...Continue Reading

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Citations

Apr 3, 2015·Journal of Cellular Biochemistry·Héctor MancillaIlona I Concha
Mar 7, 2014·Free Radical Biology & Medicine·Carola Muñoz-MontesinoCoralia I Rivas
Apr 26, 2019·Journal of Physiology and Biochemistry·Marcelo VillagránLorena Mardones
May 10, 2017·Frontiers in Oncology·Christina WohlrabGabi U Dachs
Jun 10, 2020·Cellular & Molecular Biology Letters·Magdalena Przybyło, Marek Langner
Apr 18, 2021·Journal of Food Science·Rafael ViteriAdy Giordano
Jul 4, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Marija D MiloševićZorica S Saičić

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